Targeting the CXCR4/CXCL12 Axis in Cancer Therapy: Analysis of Recent Advances in the Development of Potential Anticancer Agents.

IF 4.2 2区 化学 Q2 BIOCHEMISTRY & MOLECULAR BIOLOGY
Gerardina Smaldone, Francesca Di Matteo, Roberta Castelluccio, Valeria Napolitano, Maria Rosaria Miranda, Michele Manfra, Pietro Campiglia, Vincenzo Vestuto
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引用次数: 0

Abstract

Cancer, a leading cause of premature death, arises from genetic and epigenetic mutations that transform normal cells into tumor cells, enabling them to proliferate, evade cell death, and stimulate angiogenesis. Recent evidence indicates that chemokines are essential in tumor development, activating receptors that promote proliferation, invasion, and metastasis. The CXCR4/CXCL12 signaling pathway is gaining attention as a promising target for cancer therapy. CXCR4, a chemokine receptor, is often overexpressed in various types of cancer, including kidney, lung, brain, prostate, breast, pancreas, ovarian, and melanomas. When it binds to its endogenous ligand, CXCL12, it promotes cell survival, proliferation, and migration, crucial mechanisms for the retention of hematopoietic stem cells in the bone marrow and the movement of lymphocytes. The extensive expression of CXCR4 in cancer, coupled with the constant presence of CXCL12 in various organs, drives the activation of this axis, which in turn facilitates angiogenesis, tumor progression, and metastasis. Given the detrimental role of the CXCR4/CXCL12 axis, the search for drugs acting selectively against this protein represents an open challenge. This review aims to summarize the recent advancements in the design and development of CXCR4 antagonists as potential anticancer agents.

靶向CXCR4/CXCL12轴的肿瘤治疗:潜在抗癌药物的最新进展分析
癌症是过早死亡的主要原因,它起源于基因和表观遗传突变,这些突变将正常细胞转化为肿瘤细胞,使它们能够增殖,逃避细胞死亡,并刺激血管生成。最近的证据表明,趋化因子在肿瘤的发展中是必不可少的,它激活了促进增殖、侵袭和转移的受体。CXCR4/CXCL12信号通路作为一种有希望的癌症治疗靶点正受到关注。CXCR4是一种趋化因子受体,在各种类型的癌症中经常过度表达,包括肾癌、肺癌、脑癌、前列腺癌、乳腺癌、胰腺癌、卵巢癌和黑色素瘤。当它与内源性配体CXCL12结合时,它促进细胞存活、增殖和迁移,这是造血干细胞在骨髓中保留和淋巴细胞运动的关键机制。CXCR4在癌症中的广泛表达,加上CXCL12在各种器官中的持续存在,驱动该轴的激活,进而促进血管生成、肿瘤进展和转移。鉴于CXCR4/CXCL12轴的有害作用,寻找选择性对抗该蛋白的药物是一个公开的挑战。本文综述了近年来CXCR4拮抗剂作为潜在抗癌药物的设计和开发进展。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
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来源期刊
Molecules
Molecules 化学-有机化学
CiteScore
7.40
自引率
8.70%
发文量
7524
审稿时长
1.4 months
期刊介绍: Molecules (ISSN 1420-3049, CODEN: MOLEFW) is an open access journal of synthetic organic chemistry and natural product chemistry. All articles are peer-reviewed and published continously upon acceptance. Molecules is published by MDPI, Basel, Switzerland. Our aim is to encourage chemists to publish as much as possible their experimental detail, particularly synthetic procedures and characterization information. There is no restriction on the length of the experimental section. In addition, availability of compound samples is published and considered as important information. Authors are encouraged to register or deposit their chemical samples through the non-profit international organization Molecular Diversity Preservation International (MDPI). Molecules has been launched in 1996 to preserve and exploit molecular diversity of both, chemical information and chemical substances.
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